The lock and key analogy of receptor and substrate binding has been confirmed by x-ray crystallographic studies. These studies produce prodigious amounts of information. Recent feasibility studies have shown us that interactive computer graphics programs now in use in this laboratory make this information easily comprehensible and permit the facile manipulation of a model of a substrate molecule into the crystallographically determined model of the receptor site. Proposed modelling studies will be related to - and confirmed by - experimental (clinical, kinetic) data. Heuristics gained by this process will be used to hypothesize an unknown receptor site, which in turn will be used to postulate the design of new substrates: a rational approach to drug design. Initially, studies on two enzymes, alcohol dehydrogenase and carbonic anhydrase, will be pursued. Molecular modelling programs permit internal motions (e.g., torsional angle rotations) of amino acids and substrate molecules. Projected refinement methods (stage 1) would involve rigid units. Stage 2 would allow refinement with a flexible substrate. Stage 3 would involve complete flexibility using dynamic methods under development elsewhere. All computer programs are written in a general way. Many have been exported to a number of labs.